{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:06:34Z","timestamp":1786133194642,"version":"build-2736575974"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DK108803"],"award-info":[{"award-number":["R01DK108803"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Satellite Healthcare"},{"DOI":"10.13039\/100007880","name":"Johns Hopkins University","doi-asserted-by":"publisher","award":["Clinician Scientist Career Development Award"],"award-info":[{"award-number":["Clinician Scientist Career Development Award"]}],"id":[{"id":"10.13039\/100007880","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005326","name":"Yale University","doi-asserted-by":"publisher","award":["George M. O\u2019Brien Center for Kidney Research Pilot and Feasibility Grant"],"award-info":[{"award-number":["George M. O\u2019Brien Center for Kidney Research Pilot and Feasibility Grant"]}],"id":[{"id":"10.13039\/100005326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K08DK117068"],"award-info":[{"award-number":["K08DK117068"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Intramural Research Program, NIDDK, NIH"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01DK102134-01"],"award-info":[{"award-number":["1R01DK102134-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Veterans Affairs Puget Sound Health Care System"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2019,10]]},"abstract":"\n Significance Statement<\/jats:title>\n \n Two variations in the apo L1 gene (\n APOL1<\/jats:italic>\n ) common in West African and African American populations are strongly associated with development of ESKD. Studies evaluating whether these\n APOL1<\/jats:italic>\n kidney-risk variants increase the risk of cardiovascular disease have had inconsistent results. The authors conducted a two-stage meta-analysis of individual participant data from eight large cohorts with data on\n APOL1<\/jats:italic>\n kidney-risk variants. The analysis included 21,305 blacks and assessed the relationship between\n APOL1<\/jats:italic>\n kidney-risk variants and several types of cardiovascular disease and death. In a recessive genetic model adjusted for demographics, comorbidities, and kidney measures, there were no significant associations between\n APOL1<\/jats:italic>\n kidney-risk genotypes and death or the composite outcome of incident cardiovascular disease, which included coronary heart disease, stroke, myocardial infarction, and heart failure. There were also no significant associations between these variants and coronary heart disease, stroke, myocardial infarction, and heart failure when the conditions were considered individually. This study suggests that the\n APOL1<\/jats:italic>\n kidney-risk variants may not have a direct effect on cardiovascular disease separate from the effects of kidney disease itself.\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n \n Two coding variants in the apo L1 gene (\n APOL1<\/jats:italic>\n ) are strongly associated with kidney disease in blacks. Kidney disease itself increases the risk of cardiovascular disease, but whether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We conducted a two-stage individual participant data meta-analysis to assess the association of\n APOL1<\/jats:italic>\n kidney-risk variants with adjudicated cardiovascular disease events and death, independent of kidney measures. The analysis included 21,305 blacks from eight large cohorts.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Over 8.9\u00b15.0 years of follow-up, 2076 incident cardiovascular disease events occurred in the 16,216 participants who did not have cardiovascular disease at study enrollment. In fully-adjusted analyses, individuals possessing two\n APOL1<\/jats:italic>\n kidney-risk variants had similar risk of incident cardiovascular disease (coronary heart disease, myocardial infarction, stroke and heart failure; hazard ratio 1.11, 95% confidence interval, 0.96 to 1.28) compared to individuals with zero or one kidney-risk variant. The risk of coronary heart disease, myocardial infarction, stroke and heart failure considered individually was also comparable by\n APOL1<\/jats:italic>\n genotype.\n APOL1<\/jats:italic>\n genotype was also not associated with death. There was no difference in adjusted associations by level of kidney function, age, diabetes status, or body-mass index.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In this large, two-stage individual participant data meta-analysis,\n APOL1<\/jats:italic>\n kidney-risk variants were not associated with incident cardiovascular disease or death independent of kidney measures.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2019030240","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T15:25:14Z","timestamp":1565018714000},"page":"2027-2036","source":"Crossref","is-referenced-by-count":37,"title":["APOL1 Kidney Risk Variants and Cardiovascular Disease: An Individual Participant Data Meta-Analysis"],"prefix":"10.1681","volume":"30","author":[{"given":"Morgan E.","family":"Grams","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland;"},{"name":"Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland;"},{"name":"Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Surapaneni","sequence":"additional","affiliation":[{"name":"Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland;"},{"name":"Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoshana H.","family":"Ballew","sequence":"additional","affiliation":[{"name":"Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland;"},{"name":"Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence J.","family":"Appel","sequence":"additional","affiliation":[{"name":"Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland;"},{"name":"Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Boerwinkle","sequence":"additional","affiliation":[{"name":"Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Ebony","family":"Boulware","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, Duke University School of Medicine, Durham, North Carolina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa K.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland;"},{"name":"Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4598-0669","authenticated-orcid":false,"given":"Josef","family":"Coresh","sequence":"additional","affiliation":[{"name":"Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland;"},{"name":"Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Cushman","sequence":"additional","affiliation":[{"name":"Medicine and"},{"name":"Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Colchester, Vermont;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Divers","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Division of Public Health Sciences and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orlando M.","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Medicine and"},{"name":"Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marguerite R.","family":"Irvin","sequence":"additional","affiliation":[{"name":"Medicine and"},{"name":"Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim H.","family":"Ix","sequence":"additional","affiliation":[{"name":"Division of Nephrology-Hypertension, Department of Medicine, University of California, San Diego, California;"},{"name":"Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey B.","family":"Kopp","sequence":"additional","affiliation":[{"name":"Kidney Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis H.","family":"Kuller","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl D.","family":"Langefeld","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Division of Public Health Sciences and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Lipkowitz","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Mukamal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon K.","family":"Musani","sequence":"additional","affiliation":[{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakhi P.","family":"Naik","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology, Johns Hopkins 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